Project Summary It is estimated that 7-8% of all school-age children in the United States meet the diagnostic criteria for attention deficit hyperactivity disorder (ADHD) and the majority of these children are treated with methylphenidate (Ritalin). The percentage of school-age children treated with methylphenidate has increased steadily over the last decade and, in recent years, there has been a sharp increase in the number of preschool children given this compound. Despite the large number of children being treated with methylphenidate, surprisingly little is known about the long-term consequences of this drug. Of particular interest is the question of whether early methylphenidate treatment alters later responsiveness to rewarding or emotional stimuli. Data gathered in our laboratory indicates that methylphenidate exposure during the preweanling period (PD 11-PD 20) enhances later responsiveness to both morphine and sucrose indicating a possible change in opioid system functioning. Thus the goal of the present project is to better understand the mechanisms by which early methylphenidate treatment potentiates morphine-induced effects. To this end, we will determine whether methylphenidate exposure during the preweanling period enhances sensitivity of specific opioid receptors and whether these changes in sensitivity have a consistent effect on a variety of opioid-mediated behaviors and physiological responses. We will also assess whether early methylphenidate exposure changes the density of specific opioid receptors and whether there are concomitant changes in opioid receptor/G-protein coupling. Lastly, we will examine the long-term consequences of early methylphenidate exposure on anxiety- and depressive-like behaviors and determine whether age at drug treatment modifies these behaviors.